Genome-wide analysis of molecular changes in IL-12-induced control of mammary carcinoma via IFN-gamma-independent mechanisms. Academic Article uri icon

Overview

abstract

  • IL-12 is a major activator of tumor-killing NK cells and CTL. IFN-gamma mediates most of the well-known immunological activities of IL-12. In this study, we report IFN-gamma-independent activities induced by therapeutic application of rIL-12 in restricting tumor growth and metastasis in the 4T1 murine mammary carcinoma model. IFN-gamma-deficient mice carrying 4T1 tumor exhibit no gross defect in the number of tumor-infiltrating lymphocytes but have exaggerated angiogenesis in the tumor. Administration of IL-12 is able to constrict blood vessels in the tumor in the absence of IFN-gamma, and retains certain therapeutic efficacy even when applied late during tumor progression. IL-12 exposure in vivo does not irreversibly alter the immunogenicity of the tumor. Finally, global gene expression analysis of primary tumors reveals IL-12-induced molecular patterns and changes, implicating a number of novel genes potentially important for IFN-gamma-independent immune responses against the tumor, for IL-12-mediated antiproliferation, antimetastasis, and antiangiogenesis activities.

publication date

  • April 1, 2004

Research

keywords

  • Gene Expression Regulation, Neoplastic
  • Interferon-gamma
  • Interleukin-12
  • Mammary Neoplasms, Experimental

Identity

PubMed Central ID

  • PMC2956987

Scopus Document Identifier

  • 1642279609

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.172.7.4111

PubMed ID

  • 15034023

Additional Document Info

volume

  • 172

issue

  • 7